Extensive viral mimicry of 22 AIDS-related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS

Abstract

HIV-1 viral proteins, particularly the env protein, are homologous to 22 AIDS autoantigens, suggesting their creation by antiviral antibodies subsequently targeting human homologues. They include antibodies to T-cell receptors, CD4 and CD95, complement components, IgG, TNF and other immune-related proteins. Autoantibodies may compromise the immune system via knockdown of these key proteins, and autoimmune attack on the immune system itself, as supported by immune activation in early stages of infection and during the transition to AIDS. Over 500 human proteins contain pentapeptides or longer consensi, identical to viral peptides. Such homology explains the extensive viral/human interactome, likely related to the ability of viral homologues to compete with human counterparts as binding partners. Pathway analysis of these homologous proteins revealed their involvement in immune-related networks (e.g. natural killer cell toxicity/toll, T-cell/B-cell receptor signalling/antigen processing) and viral and bacterial entry and defence pathways (phagosome/lysosome pathways, DNA sensing/NOD/RIG-1 pathways) relevant to AIDS pathogenesis. At its inception, AIDS may have an autoimmune component selectively targeting the immune system. Immunosuppressive therapy or antibody removal, which has already achieved some success, might be therapeutically beneficial, particularly if targeted at removal of the culpable antibodies, via affinity dialysis.

Alzheimer′s Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System

“…In addition, 22 autoantigens reported in HIV-1/AIDS contain HIV-1/human matching sequences [254], supporting the contention that autoantibodies are in many cases antibodies initially raised to pathogens, which because of this homology, then target their human homologues. It has been argued that slightly dissimilar, rather than exact matches, are the more malignant in terms of autoimmunity, being less likely to be regarded as self, while the antibodies would retain low affinity for human counterparts [254,255].…”

“…In Parkinson's disease, antibodies to the Epstein-Barr virus, which has been implicated in postencephalitic adult and juvenile Parkinsonism, are also known to cross-react with synuclein, a key protein involved in neurodegeneration in this disorder [251][252][253]. In addition, 22 autoantigens reported in HIV-1/AIDS contain HIV-1/human matching sequences [254], supporting the contention that autoantibodies are in many cases antibodies initially raised to pathogens, which because of this homology, then target their human homologues. It has been argued that slightly dissimilar, rather than exact matches, are the more malignant in terms of autoimmunity, being less likely to be regarded as self, while the antibodies would retain low affinity for human counterparts [254,255].…”

Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders

“…This homology, and more particularly slightly differing rather than identical peptides (which are more likely to be recognised as nonself; Kanduc, , ), may also contribute to autoimmunity problems that are evident in many diseases. In Alzheimer's disease, multiple sclerosis, schizophrenia and AIDS, antigenic regions of several autoantigens particular to each disease are homologous to proteins expressed by the relevant suspect pathogens (Carter, , c, , c, ).…”

Toxoplasmosis and Polygenic Disease Susceptibility Genes: ExtensiveToxoplasma gondiiHost/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

“…For example, in Alzheimer's disease, multiple sclerosis, schizophrenia, and AIDS, antigenic regions of several autoantigens particular to each disease are homologous to proteins expressed by the pathogens implicated in the same disease (including T. gondii and schizophrenia) [18–21, 39]. …”

“…It has also been noted in many bioinformatics studies that pathogen proteins closely resemble our own, and that immune attack directed towards the pathogen may thus result in antibody cross-reactivity with human proteins. The development of pathogen-derived autoantibodies may also play a key role in this pathological scenario [18, 19, 21, 35–39]. …”